In silico Analysis of RpoB Sequence Variations and Rifampicin Binding Interactions in Mycobacterial Strains
Abstract
Tuberculosis (TB) remains a major global health challenge, particularly due to the increasing prevalence of multidrug-resistant and rifampicin-resistant Mycobacterium tuberculosis strains. The present study investigated sequence variation and molecular interactions of the rifampicin drug target, RNA polymerase beta subunit (RpoB), using in silico approaches. Ten RpoB protein sequences from different Mycobacterial strains showing 98–100% similarity were retrieved and analysed through multiple sequence alignment using Clustal Omega. Sequence analysis revealed conserved regions along with amino acid gaps, substitutions and truncations, particularly within functionally important regions associated with rifampicin resistance. Three-dimensional structures of all proteins were generated using SWISS-MODEL and validated by Ramachandran plot analysis, which confirmed approximately 98% residues within favoured and allowed regions indicating good stereochemical quality of the modelled structures. Rifampicin ligand preparation and molecular docking were performed using Discovery Studio 2020 with the LibDock algorithm. Docking analysis identified 39–41 active binding sites across the proteins, with binding sites 3, 5 and 6 consistently demonstrating strong molecular interactions. The highest LibDock score (137.73) was recorded for WP_003900992.1, while WP_202581977.1 showed a notable score of 120.06. Key interacting residues included arginine, glutamate, lysine, and aspartate residues,…
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